Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3

Jean M. Jennings, Dana K. Tucker, Margaret D. Kottke, Masataka Saito, Emmanuella Delva, Yasushi Hanakawa, Masayuki Amagai, Andrew P. Kowalczyk

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Pemphigus vulgaris (PV) is an epidermal blistering disorder caused by antibodies directed against the desmosomal cadherin desmoglein-3 (Dsg3). The mechanism by which PV IgG disrupts adhesion is not fully understood. To address this issue, primary human keratinocytes (KCs) and patient IgG were used to define the morphological, biochemical, and functional changes triggered by PV IgG. Three phases of desmosome disassembly were distinguished. Analysis of fixed and living KCs demonstrated that PV IgG cause rapid Dsg3 internalization, which likely originates from a non-junctional pool of Dsg3. Subsequently, Dsg3 and other desmosomal components rearrange into linear arrays that run perpendicular to cell contacts. Dsg3 complexes localized at the cell surface are transported in a retrograde manner along with these arrays before being released into cytoplasmic vesicular compartments. These changes in Dsg3 distribution are followed by depletion of detergent-insoluble Dsg3 pools and by the loss of cell adhesion strength. Importantly, this process of disassembly can be prevented by expressing exogenous Dsg3, thereby driving Dsg3 biosynthesis and desmosome assembly. These data support a model in which PV IgG cause the loss of cell adhesion by altering the dynamics of Dsg3 assembly into desmosomes and the turnover of cell surface pools of Dsg3 through endocytic pathways.

Original languageEnglish
Pages (from-to)706-718
Number of pages13
JournalJournal of Investigative Dermatology
Volume131
Issue number3
DOIs
Publication statusPublished - 2011 Mar

Fingerprint

Desmoglein 3
Desmosomes
Pemphigus
Immunoglobulin G
Cell adhesion
Keratinocytes
Cell Adhesion
Desmosomal Cadherins
Bond strength (materials)
Biosynthesis
Cadherins
Detergents

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3. / Jennings, Jean M.; Tucker, Dana K.; Kottke, Margaret D.; Saito, Masataka; Delva, Emmanuella; Hanakawa, Yasushi; Amagai, Masayuki; Kowalczyk, Andrew P.

In: Journal of Investigative Dermatology, Vol. 131, No. 3, 03.2011, p. 706-718.

Research output: Contribution to journalArticle

Jennings, Jean M. ; Tucker, Dana K. ; Kottke, Margaret D. ; Saito, Masataka ; Delva, Emmanuella ; Hanakawa, Yasushi ; Amagai, Masayuki ; Kowalczyk, Andrew P. / Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 3. pp. 706-718.
@article{df4146028c0e483eb95ab92e32d7dbee,
title = "Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3",
abstract = "Pemphigus vulgaris (PV) is an epidermal blistering disorder caused by antibodies directed against the desmosomal cadherin desmoglein-3 (Dsg3). The mechanism by which PV IgG disrupts adhesion is not fully understood. To address this issue, primary human keratinocytes (KCs) and patient IgG were used to define the morphological, biochemical, and functional changes triggered by PV IgG. Three phases of desmosome disassembly were distinguished. Analysis of fixed and living KCs demonstrated that PV IgG cause rapid Dsg3 internalization, which likely originates from a non-junctional pool of Dsg3. Subsequently, Dsg3 and other desmosomal components rearrange into linear arrays that run perpendicular to cell contacts. Dsg3 complexes localized at the cell surface are transported in a retrograde manner along with these arrays before being released into cytoplasmic vesicular compartments. These changes in Dsg3 distribution are followed by depletion of detergent-insoluble Dsg3 pools and by the loss of cell adhesion strength. Importantly, this process of disassembly can be prevented by expressing exogenous Dsg3, thereby driving Dsg3 biosynthesis and desmosome assembly. These data support a model in which PV IgG cause the loss of cell adhesion by altering the dynamics of Dsg3 assembly into desmosomes and the turnover of cell surface pools of Dsg3 through endocytic pathways.",
author = "Jennings, {Jean M.} and Tucker, {Dana K.} and Kottke, {Margaret D.} and Masataka Saito and Emmanuella Delva and Yasushi Hanakawa and Masayuki Amagai and Kowalczyk, {Andrew P.}",
year = "2011",
month = "3",
doi = "10.1038/jid.2010.389",
language = "English",
volume = "131",
pages = "706--718",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Desmosome disassembly in response to pemphigus vulgaris IgG occurs in distinct phases and can be reversed by expression of exogenous Dsg3

AU - Jennings, Jean M.

AU - Tucker, Dana K.

AU - Kottke, Margaret D.

AU - Saito, Masataka

AU - Delva, Emmanuella

AU - Hanakawa, Yasushi

AU - Amagai, Masayuki

AU - Kowalczyk, Andrew P.

PY - 2011/3

Y1 - 2011/3

N2 - Pemphigus vulgaris (PV) is an epidermal blistering disorder caused by antibodies directed against the desmosomal cadherin desmoglein-3 (Dsg3). The mechanism by which PV IgG disrupts adhesion is not fully understood. To address this issue, primary human keratinocytes (KCs) and patient IgG were used to define the morphological, biochemical, and functional changes triggered by PV IgG. Three phases of desmosome disassembly were distinguished. Analysis of fixed and living KCs demonstrated that PV IgG cause rapid Dsg3 internalization, which likely originates from a non-junctional pool of Dsg3. Subsequently, Dsg3 and other desmosomal components rearrange into linear arrays that run perpendicular to cell contacts. Dsg3 complexes localized at the cell surface are transported in a retrograde manner along with these arrays before being released into cytoplasmic vesicular compartments. These changes in Dsg3 distribution are followed by depletion of detergent-insoluble Dsg3 pools and by the loss of cell adhesion strength. Importantly, this process of disassembly can be prevented by expressing exogenous Dsg3, thereby driving Dsg3 biosynthesis and desmosome assembly. These data support a model in which PV IgG cause the loss of cell adhesion by altering the dynamics of Dsg3 assembly into desmosomes and the turnover of cell surface pools of Dsg3 through endocytic pathways.

AB - Pemphigus vulgaris (PV) is an epidermal blistering disorder caused by antibodies directed against the desmosomal cadherin desmoglein-3 (Dsg3). The mechanism by which PV IgG disrupts adhesion is not fully understood. To address this issue, primary human keratinocytes (KCs) and patient IgG were used to define the morphological, biochemical, and functional changes triggered by PV IgG. Three phases of desmosome disassembly were distinguished. Analysis of fixed and living KCs demonstrated that PV IgG cause rapid Dsg3 internalization, which likely originates from a non-junctional pool of Dsg3. Subsequently, Dsg3 and other desmosomal components rearrange into linear arrays that run perpendicular to cell contacts. Dsg3 complexes localized at the cell surface are transported in a retrograde manner along with these arrays before being released into cytoplasmic vesicular compartments. These changes in Dsg3 distribution are followed by depletion of detergent-insoluble Dsg3 pools and by the loss of cell adhesion strength. Importantly, this process of disassembly can be prevented by expressing exogenous Dsg3, thereby driving Dsg3 biosynthesis and desmosome assembly. These data support a model in which PV IgG cause the loss of cell adhesion by altering the dynamics of Dsg3 assembly into desmosomes and the turnover of cell surface pools of Dsg3 through endocytic pathways.

UR - http://www.scopus.com/inward/record.url?scp=79951518111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951518111&partnerID=8YFLogxK

U2 - 10.1038/jid.2010.389

DO - 10.1038/jid.2010.389

M3 - Article

VL - 131

SP - 706

EP - 718

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 3

ER -